scholarly journals p27 variant and corticotropinoma susceptibility: a genetic and in vitro study

2014 ◽  
Vol 21 (3) ◽  
pp. 395-404 ◽  
Author(s):  
Tomoko Sekiya ◽  
Marcello D Bronstein ◽  
Katiuscia Benfini ◽  
Viviane C Longuini ◽  
Raquel S Jallad ◽  
...  
Keyword(s):  
Cell Line ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
In Vitro Study ◽  
Mouse Cell ◽  
Endocrine Tumor ◽  
Endocrine Tumors ◽  
Parathyroid Adenomas ◽  
Acth Secreting

Abstract Germline mutations in p27kip1 are associated with increased susceptibility to multiple endocrine neoplasias (MEN) both in rats and humans; however, the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remains mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27-V109G), we genotyped a large cohort of Brazilian patients with sporadic endocrine tumors (pituitary adenomas, n=252; pheochromocytomas, n=125; medullary thyroid carcinoma, n=51; and parathyroid adenomas, n=19) and 885 population-matched healthy controls and determined the odds ratios and 95% CIs. Significant associations were found for the group of patients with pituitary adenomas (P=0.01), particularly for those with ACTH-secreting pituitary adenomas (P=0.005). In contrast, no association was found with GH-secreting pituitary tumors alone or with the sporadic counterpart of MEN2-component neoplasias. Our in vitro analyses revealed increased colony formation and cell growth rate for an AtT20 corticotropin mouse cell line overexpressing the p27-V109G variant compared with cells transfected with the WT p27. However, the genotypic effects in genetic and in vitro approaches were divergent. In accordance with our genetic data showing specificity for ACTH-secreting pituitary tissues, the overexpression of p27-V109G in a GH3 somatotropin rat cell line resulted in no difference compared with the WT. Pituitary tumors are one of the major clinical components of syndromes associated with the p27 pathogenic mutations MENX and MEN4. Our genetic and in vitro data indicate that the common polymorphism rs2066827 may play a role in corticotropinoma susceptibility and tumorigenesis through a molecular mechanism not fully understood thus far.

scholarly journals Three Dimensional Cell Culturing for Modeling Adrenal and Pituitary Tumors

2021 ◽  
Vol 27 ◽  
Author(s):  
Lilla Krokker ◽  
Borbála Szabó ◽  
Kinga Németh ◽  
Rebeka Tóháti ◽  
Balázs Sarkadi ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Pituitary Tumors ◽  
3D Cell Culture ◽  
Well Being ◽  
3D Models ◽  
Endocrine Tumor ◽  
Gh3 Cells ◽  
Endocrine Tumors ◽  
Hormone Production

In vitro monolayer conditions are not able to reproduce the complexity of solid tumors, still, there is scarce information about the 3D cell culture models of endocrine tumor types. Therefore, our aim was to develop in vitro 3D tumor models by different methodologies for adrenocortical carcinoma (H295R), pituitary neuroendocrine tumor (RC-4B/C and GH3) and pheochromocytoma (PC-12). Various methodologies were tested. Cell biological assays (cell viability, proliferation and live cell ratio) and steroid hormone production by HPLC-MS/MS method were applied to monitor cellular well-being. Cells in hanging drops and embedded in matrigel formed multicellular aggregates but they were difficult to handle and propagate for further experiments. The most widely used methods: ultra-low attachment plate (ULA) and spheroid inducing media (SFDM) were not the most viable 3D model of RC-4B/C and GH3 cells that would be suitable for further experiments. Combining spheroid generation with matrigel scaffold H295R 3D models were viable for 7 days, RC-4B/C and GH3 3D models for 7–10 days. ULA and SFDM 3D models of PC-12 cells could be used for further experiments up to 4 days. Higher steroid production in 3D models compared to conventional monolayer culture was detected. Endocrine tumor cells require extracellular matrix as scaffold for viable 3D models that can be one reason behind the lack of the usage of endocrine 3D cultures. Our models help understanding the pathogenesis of endocrine tumors and revealing potential biomarkers and therapeutic targets. They could also serve as an excellent platform for preclinical drug test screening.

scholarly journals Pituitary tumors contain a side population with tumor stem cell-associated characteristics

2015 ◽  
Vol 22 (4) ◽  
pp. 481-504 ◽  
Author(s):  
Freya Mertens ◽  
Lies Gremeaux ◽  
Jianghai Chen ◽  
Qiuli Fu ◽  
Christophe Willems ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Line ◽  
Pituitary Adenomas ◽  
Pituitary Tumor ◽  
Side Population ◽  
Pituitary Tumors ◽  
Stem Cell Marker ◽  
Tumor Stem Cell ◽  
Tumor Pathogenesis

Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial–mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP ‘main population’. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2−/−) mice that bear prolactinomas contain more pSP, Sox2+, and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.

scholarly journals Enhancing Anti-Tumoral Potential of CD-NHF by Modulating PI3K/Akt Axis in U87 Ex Vivo Glioma Model

2021 ◽  
Vol 22 (8) ◽  
pp. 3873
Author(s):  
Gabriel Luta ◽  
Mihail Butura ◽  
Adrian Tiron ◽  
Crina E. Tiron
Keyword(s):  
Cell Line ◽  
Ex Vivo ◽  
Glioma Cells ◽  
In Vitro Study ◽  
Immunofluorescent Staining ◽  
Expression Levels ◽  
Disease Diagnostics ◽  
Phosphorylated Akt ◽  
Significant Impairment

Background: In the latest years, there has been an increased interest in nanomaterials that may provide promising novel approaches to disease diagnostics and therapeutics. Our previous results demonstrated that Carbon-dots prepared from N-hydroxyphthalimide (CD-NHF) exhibited anti-tumoral activity on several cancer cell lines such as MDA-MB-231, A375, A549, and RPMI8226, while U87 glioma tumor cells were unaffected. Gliomas represent one of the most common types of human primary brain tumors and are responsible for the majority of deaths. In the present in vitro study, we expand our previous investigation on CD-NHF in the U87 cell line by adding different drug combinations. Methods: Cell viability, migration, invasion, and immunofluorescent staining of key molecular pathways have been assessed after various treatments with CD-NHF and/or K252A and AKTVIII inhibitors in the U87 cell line. Results: Association of an inhibitor strongly potentiates the anti-tumoral properties of CD-NHF identified by significant impairment of migration, invasion, and expression levels of phosphorylated Akt, p70S6Kinase, or by decreasing expression levels of Bcl-2, IL-6, STAT3, and Slug. Conclusions: Using simultaneously reduced doses of both CD-NHF and an inhibitor in order to reduce side effects, the viability and invasiveness of U87 glioma cells were significantly impaired.

In vitro study of the cytotoxic effects of microcystin-LR, cylindrospermopsin and their mixture in the neuronal SH-SY5Y cell line

2018 ◽  
Vol 295 ◽  
pp. S141
Author(s):  
M.G. Hinojosa ◽  
D. Gutierrez-Praena ◽  
A.I. Prieto ◽  
L. Espinar-López ◽  
A.M. Cameán ◽  
...  
Keyword(s):  
Cell Line ◽  
In Vitro Study ◽  
Vitro Study ◽  
Cytotoxic Effects

scholarly journals Endoscopic endonasal transsphenoidal approach for pituitary adenomas: technical aspects and report of casuistic

2010 ◽  
Vol 68 (4) ◽  
pp. 608-612 ◽  
Author(s):  
Américo Rubens Leite dos Santos ◽  
Roberto Monteiro Fonseca Neto ◽  
José Carlos Esteves Veiga ◽  
José Viana Jr ◽  
Nilza Maria Scaliassi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Hormonal Control ◽  
Subtotal Resection ◽  
Endoscopic Endonasal ◽  
Technical Aspects ◽  
Transphenoidal Approach ◽  
Acth Secreting ◽  
Csf Leaks

OBJECTIVE: Analyse technical aspects, effectiveness and morbidity of the endoscopic endonasal transphenoidal approach for pituitary adenomas. METHOD: From January 2005 to September 2008, 30 consecutive patients underwent endoscopic endonasal resection of pituitary adenomas with a follow up from 3 to 36 months. Their medical charts were retrospectively analysed. RESULTS: There were 18 women and 12 men, mean age 44 years (range 17-65 yr). Among the 30 patients, 23 had macroadenomas and 7 microadenomas. Twelve patients had non-functioning tumors, 9 had ACTH-secreting tumors, 8 had GH-secreting tumors and 1 prolactinoma. Complete resection and hormonal control was achieved in all microadenomas. Macroadenomas were completely removed in 6 patients, subtotal resection in 6 and partial resection in 11. Three patients had diabetes insipidus and 5 had CSF leaks treated with lumbar drainage. CONCLUSION: The endonasal endoscopic approach for pituitary tumors is effective and has low morbidity.

BIOAVAILABILITY OF BERYLLIUM OXIDE PARTICLES: AN IN VITRO STUDY IN THE MURINE J774A.1 MACROPHAGE CELL LINE MODEL

2005 ◽  
Vol 31 (3) ◽  
pp. 341-360 ◽  
Author(s):  
Gregory A. Day ◽  
Mark D. Hoover ◽  
Aleksandr B. Stefaniak ◽  
Robert M. Dickerson ◽  
Eric J. Peterson ◽  
...  
Keyword(s):  
Cell Line ◽  
In Vitro Study ◽  
Beryllium Oxide ◽  
Vitro Study ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Line Model ◽  
Cell Line Model ◽  
Oxide Particles

Analysis on Homoeopathic Preparation of Asterias Rubens for Evaluating Anti Breast Cancer Cell Line using Similia Principle

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 805-808
Author(s):  
Ravikumar Raju ◽  
Teja ◽  
Sravanathi P ◽  
Muthu Babu K
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
In Vitro Study ◽  
In Vivo Studies ◽  
Asterias Rubens ◽  
Mcf 7

Breast cancer is the subsequent foremost reason of cancer death in a woman and ranks as the primary foremost reason of death in India. In its conduct, several measures and recommendation are considered. Homoeopathic medicines are one of the part of a corresponding, and another medicine is utilized for the treatment of cancer. The main purpose of the investigation is to evaluate the anticancer action of homoeopathic arrangements of Asterias rubens  on the basis of the similia principle. We directed an in vitro study using MTT assay to control the result of ultra diluted homoeopathic preparation in contradiction of two human breast glandular cancer cell lines(MCF-7 and MDA-MD- 231), frequently used for the breast cancer treatment, by testing the feasibility of breast cancer (MCF-7 and MDA-MD-231) cell line, with various attenuations of Asterias rubens  at 24 hrs. Multiple comparisons between tested reagents at different concentrations confirmed the significance of the said results. At a dilution of 1:25 6CH and 30CH potency shown superior activity on MCF-7 and no such significant changes on MDA-MD-231 at any dilutions As it fails to offer estrogen receptor(ER) Also progesterone receptor (PR) expression, and also HER2 (human epidermal development variable receptor2) so continuously a triple-negative breast cancer it will be a hostility manifestation for breast cancer with restricted medicine choices. However, further potency needs to be tested. These preliminary significant results warrant further in vitro and in vivo studies to estimate the possible of Asterias rubens  a medicine to treat breast cancer.

Sign in / Sign up

Export Citation Format

Share Document